Page 106 - 《中国药科大学学报》2025年第4期

502 学报 Journal of China Pharmaceutical University 2025, 56(4): 498 − 506 第 56 卷
A Vehicle Metoprolol

day1 day2
1 h calculation 1 h calculation
B 60 * *** *** E 30
Total wakefulness time/min 40 * Wakefulness bouts 20 *

20
10

0 0
5 10 20 40 80 5 10 20 40 80
Dosage/(mg/kg) Dosage/(mg/kg)
C 50 * * *** *** F 20 **
Total NREMS time/min 30 NREMS bouts 10
40
15

20
5
10
0 0
5 10 20 40 80 5 10 20 40 80
Dosage/(mg/kg) Dosage/(mg/kg)
D 8 G 8 **
** **
*
Total REMS time/min 4 2 * REMS bouts 4 *
**
*
6
6
*
2

0 0
5 10 20 40 80 5 10 20 40 80
Dosage/(mg/kg) Dosage/(mg/kg)
H 30

Micro arousal No. 20 * Vehicle_Adrb1 ; +/+
+/+
Metoprolol_Adrb1 ;
+/m
Vehicle_Adrb1 ;
10
Metoprolol_Adrb1
+/m
0
5 10 20 40 80
Dosage/(mg/kg)
Figure 1 Intraperitoneal metoprolol injection increases wakefulness
A： Schematic workflow of experiment setup. (B-H) The sleep/wake status of wild-type mice (n=11) and mutant mice (n=9,5mg/kg;
n=7,10mg/kg; n=10,20mg/kg; n=8,40mg/kg; n=10,80mg/kg) within 1 hour after administration were calculated for wakefulness duration
(B), NREMS duration (C) , REMS duration (D), wakefulness bouts (E), NREMS bouts (F) ,REMS bouts (G) and micro arousal numbers
(H) . * P<0.05, **P<0.01, ***P<0.001. Two-Way ANOVA, post-hoc Sidak's multiple comparisons test. Three-Way ANOVA to compare the
differences between genotypes
没有观察到觉醒或 NREM 睡眠发作次数的显著变 显著减少 REM 睡眠持续时间和发作次数（图 5-G，

化（图 5-K，5-L）。使用普萘洛尔和比索洛尔均可 5-M），提示 β 受体阻断药普遍对 REM 睡眠的发生